The present invention relates to attenuated variants of the fungus B. dermatitidis, and methods of using them to vaccinate against the wild type fungus.
Blastomycosis is a disease caused by infection with the fungus Blastomyces dermatitidis. Humans and other animals (particularly dogs) can be infected by inhaling aerosolized fungal spores from, for example, soil where the organism dwells. At body temperature, these spores convert to yeast forms. Acute primary pulmonary infection caused by the yeast can produce an influenza or pneumonia syndrome. Progressive forms of the disease can cause serious damage to the lungs, skin, bones, joints, or prostate gland.
It is therefore desirable to develop a vaccine against this disease. In U.S. Pat. No. 5,093,118 (the disclosure of this patent and all other publications referred to herein being incorporated by reference as if fully set forth herein) we described the isolation of a cell wall protein of the fungus B. dermatitidis that we named WI-1. It was suggested that this protein be used in a vaccine for Blastomycosis.
In U.S. Pat. No. 5,302,530 we described the coding DNA for this protein. While WI-1 has been of some value in raising antigenic responses, its impact on long-term survival of hosts challenged with certain strains of the wild type fungus has not been sufficient. Thus, efforts have continued to try to find more widely effective vaccines against this disease.
In unrelated work, fluorescence staining of the fungal surface and extractions of cell wall proteins have shown that WI-1 can be expressed to a lower extent in genetically related strains having higher virulence. B. Klein et al., 62 Infect. Immun. 3536-3542 (1994). If anything, this would have taught away from trying to delete WI-1 expression as a means of attenuating a fungus.
It should also be noted that we recently published techniques for genetically manipulating B. dermatitidlis by using DNA mediated gene transfer. See L. Hogan et al., 186 Gene 219-226 (1997).
To date we are unaware of anyone having successfully obtained an attenuated replication competent B. dermatitidis fungal vaccine, or any other vaccine against this fungus (e.g. protein based, DNA based, or otherwise) which meets the needs in this art. Thus, a need exists for an improved vaccine against B. dermatitidis.